Retinol structure

Figure S.3 Schematic diagram of the structure of human plasma retinol-binding protein (RBP), which is an up-and-down P barrel. The eight antiparallel P strands twist and curl such that the structure can also be regarded as two p sheets (green and blue) packed against each other. Some of the twisted p strands (red) participate in both P sheets. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two P sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule. The topological diagram of this stmcture is the same as that in Figure 5.2. (Courtesy of Alwyn Jones, Uppsala, Sweden.)...

The retinol-binding protein belongs to a superfarnily of protein structures... 

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

Godovac-Zimmerman, J. The structural motif of p-lactoglobulin and retinol-binding protein a basic framework for binding and transport of small hydrophobic molecules Trends Biochem. Sci. 

Newcomer, M.E., et al. The three-dimensional structure of retinol-binding protein. EMBO J. 

In rhino viruses there are depressions, or "canyons," which are 25 A deep and 12 to 30 A wide and which encircle the protrusions (Figure 16.15b). One wall of the canyons is lined by residues from the base of VPl. The structure of VPl is such that the barrel is open at the base and permits access to the hydrophobic interior of the barrel, as in the up-and-down barrel structure of the retinol-binding protein described in Chapter 5. 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

The carotenoids are the most widely distributed group of pigments, occur naturally in large quantities, and are known for their structural diversity and various functions. The carotenoids constitnte a widespread class of natural pigments that occur in all three domains of life in the eubacteria, the archea, and the eucarya. Carotenoids are ubiquitous organic molecules, but they are not produced by the human body. They have been fonnd to be essential to human health based on the nutritional understanding of vitamin A (retinol) and (i-carotene. ... 

It is assumed that in order to have vitamin A activity a molecule must have essentially one-half of its structure similar to that of (i-carotene with an added molecule of water at the end of the lateral polyene chain. Thus, P-carotene is a potent provitamin A to which 100% activity is assigned. An unsubstituted p ring with a Cii polyene chain is the minimum requirement for vitamin A activity. y-Car-otene, a-carotene, P-cryptoxanthin, a-cryptoxanthin, and P-carotene-5,6-epoxide aU have single unsubstimted rings. Recently it has been shown that astaxanthin can be converted to zeaxanthin in trout if the fish has sufficient vitamin A. Vitiated astaxanthin was converted to retinol in strips of duodenum or inverted sacks of trout intestines. Astaxanthin, canthaxanthin, and zeaxanthin can be converted to vitamin A and A2 in guppies. ... 

Kennedy, M.W., Garside, L.H., Goodrick, L.E., McDermott, L., Brass, A., Price, N.C., Kelly, S.M., Cooper, A. and Bradley, J.E. (1997) The Ov20 protein of the parasitic nematode Onchocerca volvulus. A structurally novel class of small helix-rich retinol-binding protein. Journal of Biological Chemistry 272, 29442-29448. 

Vitamin Ai (retinol) is derived in mammals by oxidative metabolism of plant-derived dietary carotenoids in the liver, especially -carotene. Green vegetables and rich plant sources such as carrots help to provide us with adequate levels. Oxidative cleavage of the central double bond of -carotene provides two molecules of the aldehyde retinal, which is subsequently reduced to the alcohol retinol. Vitamin Ai is also found in a number of foodstuffs of animal origin, especially eggs and dairy products. Some structurally related compounds, including retinal, are also included in the A group of vitamins. 

Vitamin A, or retinol, is essential for the proper maintenance of the functional and structural integrity of epithelial cells, and it plays a major role in epithelial dif-... 

Since its discovery in 1909, the elucidation of its structure by Karrer in 1931 [5] and its first total synthesis [6], vitamin A has represented a challenging target molecule for chemists [7], The first industrial synthesis of retinol was performed at Hoffmann-La Roche (H-L R) [8], followed by other approaches of the Baadische Anilin- Soda Fabrik (BASF AG) [9], and Rhone-Poulenc (R-P) (today Aventis) [10]... 

Chen LC, Berberian I, Koch B, et al. 1992. Polychlorinated and polybrominated biphenyl congners and retinol levels in rat tissues Structural-activity relationships. Toxicol Appl Pharmacol 114(l) 47-55. 

This method requires the least sophisticated equipment and relies heavily on the unique characteristics of the column to separate the carotenoids (Craft et al., 1992 Epler et al., 1992). It incorporates the use of a polymeric Cl 8 column, which has been shown to offer unique selectivity for structurally similar compounds such as geometric isomers. The addition of a second detector or use of a diode-array detector permits the simultaneous analysis of tocopherols, but not retinol. If the method is modified to incorporate a solvent gradient, retinol can be measured also (MacCrehan and Schonberger, 1987). 

From a nutritional viewpoint, the carotenoids are classified as provitamins and inactive carotenoids. To have vitamin A activity, the carotenoid molecule must incorporate a molecule of retinol, i.e., an unsubstituted /3-ionone ring with an 11-carbon polyene chain. /3-carotene (C40H56, MW = 536.88), the most ubiquitous provitamin A carotenoid, is composed of two molecules of retinol joined tail to tail thus the compound possesses maximal (100%) vitamin A activity. The structures of all other provitamin A carotenoids incorporate one molecule of retinol and hence theoretically contribute 50% of the biological activity of /3-carotene. Among the 600 or so carotenoids that exist in nature, only about 50 possess vitamin A activity in varying degrees of potency. 

Figure S2.4 shows the structures of 11 -c/.v-retinal and its more stable isomer all-frans-retinal. The reti-nals are related to the alcohol retinol, or vitamin A,. Mammals cannot synthesize these compounds de novo but can form them from dietary carotenoids such as /3-carotene. A deficiency of vitamin A causes night blindness, along with serious deterioration of the eyes and other tissues.

Structures of retinals, retinols, and 13-carotene. The structure of 11 -cis-retinal (top) indicates the numbering system used for the carbons. In rhodopsin, 11 -a. s-retinal is bound by a protonated Schiff s base linkage to a lysine of opsin. 

Figure 2. General structure of retinoic acid (all trans-retinoic acid). Of the many derivatives tested (e.g., retinol, retinyl acetate), none has the "anti-tumor promoter efficacy, in vivo, as retinoic acid.

The A group of vitamins are important metabolites of carotenoids. Vitamin A, (retinol) (Figure 5.70) effectively has a diterpene structure, but it is derived in mammals by oxidative... 

Although the term vitamin A has been used to denote specific chemical compounds, such as retinol or its esters, this term now is used more as a generic descriptor for compounds that exhibit the biological properties of retinol. Retinoid refers to the chemical entity retinol or other closely related naturally occurring derivatives. Retinoids also include structurally related synthetic analogues, which need not have retinol-like (vitamin A) activity. The structural formulas for the vitamin A family of retinoids are shown in Figure 66.3. Retinol (vitamin Aj), a primary alcohol, is present in esterihed form in the tissues of animals and saltwater fish, mainly in the liver. A closely related compound, 3-dehydroretinol (vitamin A2), is obtained from the tissues of freshwater fish and usually occurs mixed with retinol. 

Ethers and esters derived from the alcohol also show activity in vivo. The ring structure of retinol ((i-ionone), or the more unsaturated ring in 3-dehydroretinol (dehydro-P-ionone), is essential for activity hydrogenation destroys biological activity. Of all known derivatives, all-/ran,v-retinol and its aldehyde, retinal, exhibit the greatest biological potency in vivo 3-dehydroretinol has about 40% of the potency of all-bms-retinol. 

The lipase-catalysed hydrolysis of methyl 2-fluoro-2-arylpropionates was proposed to proceed via a mechanism whereby, after ester hydrolysis, the enzyme facilitates the elimination of fluoride ion with the formation of a carbocation stabilized by the adjacent C02 group.230 Determination of the crystal structure of human sialidase Neu2, an enzyme that catalyses the hydrolysis of sialic acids, reveals a tyrosine residue that is positioned in the active site to stabilize the carbocation proposed as an intermediate in the hydrolysis.231 ll-Fluoro-all-frans-retinol is found to undergo isomerization to its 11 -cis form in the presence of visual cycle enzymes, in contrast to a previous study where no isomerization was reported.232 The result of the prior study was taken as evidence for a carbonium ion pathway in the isomerization. Although the authors of the present study do not rule out such a mechanism, they suggest that the isomerization mechanism remains unknown. Data obtained in a study of the oxidation of... 

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